X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency disease of phagocytes caused by mutations in the cytochrome b(558)β (CYBB) gene.
We report here two atypical cases of X-linked CGD patients (first cousins) in which cytochrome b(558) is present at a normal level but is not functional (X91+).
Missense mutations in the gp91-phox gene encoding cytochrome b558 in patients with cytochrome b positive and negative X-linked chronic granulomatous disease.
Since the genetic mutation responsible for this type of CGD results in the absence of cytochrome b-558 in PMNs, fibroblasts should be affected in the same way if both cytochrome species were identical.
A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease.
Variant X-linked chronic granulomatous disease (CGD) is characterised by a decreased but still measurable respiratory burst and cytochrome b content of phagocytes resulting in a clinically milder form of the disease.
Phagocytes from X-linked chronic granulomatous disease (X-CGD) patients are deficient in their ability to generate superoxide because of a defective gene that encodes a heavy chain of cytochrome b, a critical component in the superoxide-generating pathway.
In association with these functional changes, we observed an increase in cellular contents of phagocyte cytochrome b (a critical component of the superoxide-producing oxidase) and immunoreactive cytochrome b heavy chain (the product of the gene that is defective in X-linked chronic granulomatous disease).
Cytochrome b-245 is the only clearly defined component of this oxidase system and its absence provides the molecular basis of X-linked chronic granulomatous disease (CGD), in which a profound predisposition to infection results from complete failure of this respiratory burst.
Somatic cell hybridization was performed between the monocytes from the affected boy in this family with monocytes from either a cytochrome b-negative male patient with X-linked chronic granulomatous disease or a cytochrome b-positive male patient with the classic autosomal form of this disease.